Methods and materials for discovery of functional ligands to molecular complexes

Abstract

This invention relates to methods and materials for discovery of functional ligands, particularly to methods and materials for selecting for functional ligands to molecular complexes, and more particularly to methods and materials for selecting for functional ligands to molecular complexes with metal ions, such as coordination complexes with metal ions. For example, functional ligands, such as aptamers, may be selected for specific and high affinity binding to coordination complexes of metal ions of interest, such as particular arsenic ions.

The invention claimed is: 
     
       1. A method for selecting functional ligands comprising:
 providing a library of biomolecules; 
 contacting said library with a target, said target comprising a target ionic species comprising arsenic (III) ion complexed with a coordination compound, said coordination compound selected from the group consisting of 4-(mercaptomethyl)benzoic acid, 1,4-benzenedimethanethiol, meso-2,3-dimercaptosuccinic acid, 2,3-dimercapto-1-propanesulfonic acid, and 2,3-dimercapto-1-propanol; 
 sequestering members of said library which bind to said target, wherein said members bind via non-Watson-Crick and non-covalent binding; 
 determining the composition or sequence of said members which bind to said target. 
 
     
     
       2. The method of  claim 1 , further comprising an enrichment step of contacting said members which bind to said target with said target and sequestering members of said library which bind again to said target prior to determining the composition or sequence for a number of times. 
     
     
       3. The method of  claim 1 , wherein said biomolecules are selected from the group consisting of single-stranded nucleic acids, peptide molecules and artificially modified versions thereof. 
     
     
       4. The method of  claim 1 , wherein said members which bind to said target comprise non-naturally occurring nucleic acid sequences. 
     
     
       5. The method of  claim 1 , wherein said target ionic species is protected from oxidation by addition of an antioxidant. 
     
     
       6. The method of  claim 1 , wherein said target ionic species is protected from oxidation by addition of ascorbic acid. 
     
     
       7. The method of  claim 1 , wherein said target is a molecular complex with the form selected from the group consisting of As 2 L 2  or As 2 L 3 . 
     
     
       8. The method of  claim 1 , wherein said coordination compound adopts a conformation when complexed with said target ionic species via reversible arsenic (III) to sulphur bond(s). 
     
     
       9. The method of  claim 1 , wherein said coordination compound adopts a conformation when complexed with said target ionic species comprising a trigonal-pyramidal geometry. 
     
     
       10. The method of  claim 4 , enrichment step enriches for members which bind at a higher affinity than said members prior to said enrichment step.